Structural insight into mitochondrial β-barrel outer membrane protein biogenesis
Structural insight into mitochondrial β-barrel outer membrane protein biogenesis
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DOI：
10.1038/s41467-020-17144-1
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发表时间：
2020-07-03
影响因子：
16.6
通讯作者：
Buchanan, Susan K.
中科院分区：
文献类型：
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作者：
Diederichs, Kathryn A.;Ni, Xiaodan;Buchanan, Susan K.
在线粒体中，β -桶状外膜蛋白介导蛋白质输入、代谢物转运、脂质转运和生物发生。分选与组装机器（SAM）复合物由三种蛋白质组成，它们以1:1:1的复合物形式组装，以折叠β -桶状蛋白并将其插入线粒体外膜。我们报道了来自嗜热毁丝霉（Myceliophthora thermophila）的SAM复合物的冷冻电镜结构，其显示Sam50形成一个16链的跨膜β -桶，具有一个延伸到膜间隙的单一多肽转运相关（POTRA）结构域。Sam35和Sam37位于外膜的胞质侧，Sam35覆盖在Sam50上，Sam37与Sam35广泛相互作用。Sam35和Sam37各自采用一种类似谷胱甘肽S -转移酶（GST）的折叠结构，与它们在细菌中的对应物没有功能、结构或序列相似性。结构分析表明Sam50的β -桶如何打开一个侧向门以容纳其底物。分选与组装机器（SAM）复合物折叠β -桶状蛋白并将其插入线粒体外膜。在此，作者报道了来自嗜热毁丝霉的SAM复合物的冷冻电镜结构，该结构揭示了Sam35和Sam37类似谷胱甘肽S -转移酶的折叠结构，并阐明了Sam50的β -桶如何打开一个侧向门以容纳其底物。
In mitochondria, beta -barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold beta -barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane beta -barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 beta -barrel opens a lateral gate to accommodate its substrates. The Sorting and Assembly Machinery (SAM) complex folds beta-barrel proteins and inserts them into the mitochondrial outer membrane. Here authors report cryoEM structures of the SAM complex from Myceliophthora thermophila, which reveals a GST-like fold for Sam35 and Sam37 and sheds light on how the Sam50 beta-barrel opens a lateral gate to accommodate its substrates.